Clinical pitfalls related to short and long echo times in cerebral MR spectroscopy.

MR-spectroscopy (MRS) is a multiparameter diagnostic tool and modification of each parameter results in spectrum morphology changes. In particular, changing the echo time (TE) represents a useful tool to highlight different diagnostic elements, but also has significant impact on the spectrum morphology. Diagnostic errors can result if the role of TE is not properly considered. This article reviews the four most common TE-related pitfalls of MRS interpretation. Clinical practical methods to avoid such pitfalls are also suggested.

Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans.

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Involvement of striate and extrastriate visual cortical areas in spatial attention.

We investigated the cortical mechanisms of visual-spatial attention while subjects discriminated patterned targets within distractor arrays. Functional magnetic resonance imaging (fMRI) was used to map the boundaries of retinotopic visual areas and to localize attention-related changes in neural activity within several of those areas, including primary visual (striate) cortex. Event-related potentials (ERPs) and modeling of their neural sources, however, indicated that the initial sensory input to striate cortex at 50-55 milliseconds after the stimulus was not modulated by attention. The earliest facilitation of attended signals was observed in extrastriate visual areas, at 70-75 milliseconds. We hypothesize that the striate cortex modulation found with fMRI may represent a delayed, re-entrant feedback from higher visual areas or a sustained biasing of striate cortical neurons during attention. ERP recordings provide critical temporal information for analyzing the functional neuroanatomy of visual attention.

Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases.

OBJECTIVE: To determine cerebral energy status in patients with Huntington's disease (HD) and Parkinson's disease (PD). METHODS: The study included 15 patients with DNA-proven, symptomatic HD and five patients with medically treated, idiopathic PD, all of whom were candidates for neurotransplant treatment, as well as 20 age-related normal subjects. Quantitative noninvasive, MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia (BG), occipital gray matter, and posterior parietal white matter; in addition, quantitative phosphorus and proton-decoupled phosphorus MRS of superior biparietal white and gray matter was done. Outcome measures were quantitative metabolite ratios and millimolar concentrations of neuronal and glial markers, creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. RESULTS: In volume-corrected control BG (10.46 +/- 0.37 mM), [Cr] was 29% (p < 0.05) higher than in control gray matter (8.10 +/- 1.04 mM). In HD and PD, energy metabolism was not abnormal in the four cerebral locations measured by MRS. No increase in cerebral lactate or decrease in phosphocreatine and ATP was detected. Small, systematic abnormalities in N-acetylaspartate (NAA, decreased), Cr (decreased), choline-containing compounds (Cho, increased), and myoinositol (mI, increased) were demonstrable in all patient's individually and in summed spectra but were insufficient to make diagnosis possible in the individual patient. CONCLUSION: Previously described failure of global energy metabolism in HD was not confirmed. However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are sensitive to +/-10% alterations in key cerebral metabolites, and may be of value in noninvasive monitoring of appropriate therapies.

High resolution magnetic resonance imaging of the brain in the dy/dy mouse with merosin-deficient congenital muscular dystrophy.

Magnetic resonance imaging (MRI) abnormalities in the cerebral white matter are a consistent feature of merosin-deficient human congenital muscular dystrophy, a disease caused by a primary defect in the expression of the laminin alpha2 chain of merosin. To investigate the relationship between imaging changes and merosin deficiency we undertook a MRI study in the dy/dy mouse, an animal model for this form of human congenital muscular dystrophy. High resolution in vivo imaging was performed on anaesthetized animals (two homozygous dy/dy mutants and two heterozygous dy/DY controls, aged 2.5 months) in a dedicated 11.7T magnetic resonance imaging scanner. T(1) and T(2) weighted images were normal in all mice and white matter changes were not seen at a stage of maturity when MRI changes are already very striking in human patients. Cerebral MRI abnormalities do not appear to be a feature of dy/dy mice, despite the virtual absence of merosin expression in the dy/dy mouse brain. Possible causes for this absence of MRI changes, and implications for the pathogenesis of the MRI changes in humans are reviewed.

Enhancing fMRI contrast in awake-behaving primates using intravascular magnetite dextran nanopartieles.

Functional MRI in awake-behaving primates is an emerging tool for bridging the gap between human fMRI and neurophysiology information from nonhuman primates. We report the use of magnetite dextran nanoparticles (Feridex) as a blood-pool agent to enhance fMRI contrast-to-noise (CNR) in primate FMRI. The intravascular half-life of the magnetite dextran was long compared to lanthanide chelates (T(1/2) = 198 min) with shortened T(2) relaxation observed in blood and cerebral cortex. Greater than 3-fold enhancement in the percentage MR signal change was observed using nanoparticles (13%) compared with conventional BOLD fMRI (4%). The calculated regional cerebral blood volume in macaque primary visual cortex increased 32% with photic stimulation. The increased CNR allows greater flexibility in the design of awake-behaving primate fMRI studies with the potential for improvements in resolution and significantly shortened imaging times.

Functional magnetic resonance imaging in macaque cortex.

The ability to use fMRI in a monkey model would bridge the gap between the fMRI demonstration of cerebral activation in humans and the cumulative wealth of monkey data on the functional organization of the brain from single electrode mapping, radioisotope and histology studies. We report a new technique for fMRI in an awake co-operative rhesus macaque (Macaca mulatta) in a conventional clinical 1.5T MR scanner and present the first fMRI images from a macaque. Good resolution, signal-to-noise ratio and BOLD response (2.6-4.6%) have been achieved using the manufacturer's standard volume knee coil. T1 values of macaque gray and white matter (1490 ms, 1010 ms respectively) are higher than human brain, whereas T2 values are lower (55 ms, 48 ms respectively). An MR-compatible design for restraining the monkey is also described, along with a suitable EPI sequence for BOLD images, optimized for monkey T2, with voxel sizes from 29 to 61 microl, and MPRAGE sequence for anatomical studies with 0.8 mm isotropic resolution, optimized for monkey T1.

Magnetic resonance image-guided implantation of chronic recording electrodes in the macaque intraparietal sulcus.

The implantation of chronic recording electrodes in the brain has been shown to be a valuable method for simultaneously recording from many neurons. However, precise placement of these electrodes, crucial for successful recording, is challenging if the target area is not on the brain surface. Here we present a stereotaxic implantation procedure to chronically implant bundles of recording electrodes into macaque cortical sulci, employing magnetic resonance (MR) imaging to determine stereotaxic coordinates of target location and sulcus orientation. Using this method in four animals, we recorded simultaneously the spiking activity and the local field potential from the parietal reach region (PRR), located in the medial bank of the intraparietal sulcus (IPS), while the animal performed a reach movement task. Fifty percent of all electrodes recorded spiking activity during the first 2 post-operative months, indicating their placement within cortical gray matter. Chronic neural activity was similar to standard single electrode recordings in PRR, as reported previously. These results indicate that this MR image-guided implantation technique can provide sufficient placement accuracy in cortical sulci and subcortical structures. Moreover, this technique may be useful for future cortical prosthesis applications in humans that require implants within sulci.

Direct comparison of visual cortex activation in human and non-human primates using functional magnetic resonance imaging.

We report a technique for functional magnetic resonance imaging (fMRI) in an awake, co-operative, rhesus macaque (Macaca mulatta) in a conventional 1.5T clinical MR scanner, thus accomplishing the first direct comparison of activation in visual cortex between humans and non-human primates with fMRI. Activation was seen in multiple areas of striate and extra-striate visual cortex and in areas for motion, object and face recognition in the monkey and in homologous visual areas in a human volunteer. This article describes T1, T2 and T2* values for macaque cortex, suitable MR imaging sequences, a training schedule, stimulus delivery apparatus and restraining hardware for monkey fMRI using a conventional 19 cm knee coil. Much of our understanding of the functional organization of the primate brain comes from physiological studies in monkeys. Direct comparison between species using fMRI such as those described here will help us to relate the wealth of existing knowledge on the functional organization of the non-human primate brain to human fMRI.

MR of hypoxic encephalopathy in children after near drowning: correlation with quantitative proton MR spectroscopy and clinical outcome.

BACKGROUND AND PURPOSE: Quantitative MR spectroscopy has a proved role in the investigation of hypoxia caused by near drowning. To date, no studies have addressed the MR imaging changes that may also accompany this condition. The purpose of this study was to describe the MR imaging findings in children with hypoxic encephalopathy caused by near drowning and to compare these findings with the results of qualitative and quantitative proton MR spectroscopy and clinical outcome. METHODS: Twenty-two children (6 months to 11 years old) admitted to the pediatric intensive care unit after near drowning incidents underwent cerebral MR imaging and quantitative proton MR spectroscopy. Clinical and imaging studies were reviewed retrospectively, and subjects were grouped according to outcome: good result, persistent vegetative state, and death. Images were scored for edema, basal ganglia changes, and cortical changes, and were compared with MR spectra and outcome at days 1 to 2, 3 to 4, and 5 or more. RESULTS: Six patients had a good outcome, four remained in a persistent vegetative state, and 12 died. Generalized/occipital edema correlated with poor outcome. Indistinct lentiform nuclei margins on T1-weighted images were a frequent finding (78%). Basal ganglia T2 hyperintensity correlated with poor outcome, progressing from a patchy/peripheral distribution to diffuse high intensity. Patchy high T2 signal in the cortex or subcortical lines were specific but insensitive for poor outcome, as were brain stem infarcts. CONCLUSION: MR images in children with hypoxic encephalopathy after near drowning show a spectrum of changes. The most sensitive prognostic result may be achieved by combining MR imaging with qualitative and quantitative MR spectroscopic data.

Technical note: bone SPECT of the wrist.

A technique for single photon emission computed tomography (SPECT) during bone scintigraphy of the wrist is described. The technique has been developed as a means to improve localization of abnormalities observed on 99Tcm-MDP planar bone scintigraphy. A wrist phantom and 15 wrists in 13 symptomatic patients were examined. Good spatial detail was achieved, with the pisiform readily identifiable as a separate bone in six wrists. In seven cases the tomograms permitted better localization of planar image abnormalities and in four cases additional lesions were visible which were missed on planar scintigraphy. This technique can be applied to all patients with suspected carpal injury and allows better anatomical localization and greater sensitivity than planar scintigraphy alone.

The effect of supine exercise on the distribution of regional pulmonary blood flow measured using proton MRI.

The Zone model of pulmonary perfusion predicts that exercise reduces perfusion heterogeneity because increased vascular pressure redistributes flow to gravitationally nondependent lung, and causes dilation and recruitment of blood vessels. However, during exercise in animals, perfusion heterogeneity as measured by the relative dispersion (RD, SD/mean) is not significantly decreased. We evaluated the effect of exercise on pulmonary perfusion in six healthy supine humans using magnetic resonance imaging (MRI). Data were acquired at rest, while exercising (∼27% of maximal oxygen consumption) using a MRI-compatible ergometer, and in recovery. Images were acquired in most of the right lung in the sagittal plane at functional residual capacity, using a 1.5-T MR scanner equipped with a torso coil. Perfusion was measured using arterial spin labeling (ASL-FAIRER) and regional proton density using a fast multiecho gradient-echo sequence. Perfusion images were corrected for coil-based signal heterogeneity, large conduit vessels removed and quantified (in ml·min(-1)·ml(-1)) (perfusion), and also normalized for density and quantified (in ml·min(-1)·g(-1)) (density-normalized perfusion, DNP) accounting for tissue redistribution. DNP increased during exercise (11.1 ± 3.5 rest, 18.8 ± 2.3 exercise, 13.2 ± 2.2 recovery, ml·min(-1)·g(-1), P < 0.0001), and the increase was largest in nondependent lung (110 ± 61% increase in nondependent, 63 ± 35% in mid, 70 ± 33% in dependent, P < 0.005). The RD of perfusion decreased with exercise (0.93 ± 0.21 rest, 0.73 ± 0.13 exercise, 0.94 ± 0.18 recovery, P < 0.005). The RD of DNP showed a similar trend (0.82 ± 0.14 rest, 0.75 ± 0.09 exercise, 0.81 ± 0.10 recovery, P = 0.13). In conclusion, in contrast to animal studies, in supine humans, mild exercise decreased perfusion heterogeneity, consistent with Zone model predictions.

Pulmonary perfusion heterogeneity is increased by sustained, heavy exercise in humans.

Exercise presents a considerable stress to the pulmonary system and ventilation-perfusion (Va/Q) heterogeneity increases with exercise, affecting the efficiency of gas exchange. In particular, prolonged heavy exercise and maximal exercise are known to increase Va/Q heterogeneity and these changes persist into recovery. We hypothesized that the spatial heterogeneity of pulmonary perfusion would be similarly elevated after prolonged exercise. To test this, athletic subjects (n = 6, Vo(2max) = 61 ml. kg(-1).min(-1)) with exercising Va/Q heterogeneity previously characterized by the multiple inert gas elimination technique (MIGET), performed 45 min of cycle exercise at approximately 70% Vo(2max). MRI arterial spin labeling measures of pulmonary perfusion were acquired pre- and postexercise (at 20, 40, 60 min post) to quantify the spatial distribution in isogravitational (coronal) and gravitationally dependent (sagittal) planes. Regional proton density measurements allowed perfusion to be normalized for density and quantified in milliliters per minute per gram. Mean lung density did not change significantly in either plane after exercise (P = 0.19). Density-normalized perfusion increased in the sagittal plane postexercise (P =or <0.01) but heterogeneity did not (all P >or= 0.18), likely because of perfusion redistribution and vascular recruitment. Density-normalized perfusion was unchanged in the coronal plane postexercise (P = 0.66), however, perfusion heterogeneity was significantly increased as measured by the relative dispersion [RD, pre 0.62(0.07), post 0.82(0.21), P < 0.0001] and geometric standard deviation [GSD, pre 1.74(0.14), post 2.30(0.56), P < 0.005]. These changes in heterogeneity were related to the exercise-induced changes of the log standard deviation of the ventilation distribution, an MIGET index of Va/Q heterogeneity (RD R(2) = 0.68, P < 0.05, GSD, R(2) = 0.55, P = 0.09). These data are consistent with but not proof of interstitial pulmonary edema as the mechanism underlying exercise-induced increases in both spatial perfusion heterogeneity and Va/Q heterogeneity.

Problem in diagnostic imaging.

The staging of malignant disease for metastatic spread requires a sound understanding of the normal anatomy and possible anatomical variants as well as the expected pathology. This article illustrates this in the case of a young man with seminoma of the testis undergoing CT imaging to assess for para-aortic metastatic spread. A potential pitfall that may mislead the unwary is demonstrated.

Peripheral somatosensory fMRI in mouse at 11.7 T.

The feasibility of performing extremely-high resolution somatosensory fMRI in anesthetized mice using BOLD contrast at 11.7 T was investigated. A somatosensory stimulus was applied to the hindlimb of an alpha-chlorolose anesthetized mouse resulting in robust (p < 4 x 10(-3)) BOLD changes in somatosensory cortex and large veins. Percentage modulation of the MR signal in cortex exceeded 7%. Experiments that artificially modulated the inspired oxygen tension were also conducted; the results revealed large, heterogeneous, BOLD contrast changes in the mouse brain. In addition, T(1), T(2), and T(2)* values in gray matter at 11.7 T were evaluated. Discussion of the sensitivity limitations of BOLD fMRI in the tiny mouse central nervous system is presented. These methods show promise for the assessment of neurological function in mouse models of CNS injury and disease.